Methods for treating diabetic wounds

Abstract

The present invention relates to a method of treating chronic wounds using calreticulin. In particular, the invention relates to the treatment of chronic diabetic wounds using topical application of calreticulin to a patient in need of such treatment.

The invention claimed is: 
     
       1. A method for treating a chronic wound of a mammal, which comprises topically administering to the wound a therapeutically effective amount of a functional fragment of a mammalian calreticulin, wherein the functional fragment is the N-, P- or C-domain of a mammalian calreticulin. 
     
     
       2. The method of  claim 1 , wherein the chronic wound is a chronic diabetic wound. 
     
     
       3. The method of  claim 2 , wherein the chronic diabetic wound is a diabetic foot ulcer. 
     
     
       4. The method of  claim 1 , wherein said functional fragment is administered in an amount between about 0.001 milligram and about 1 gram. 
     
     
       5. The method of  claim 4 , wherein said functional fragment is administered in an amount between about 0.01 milligram and about 50 milligrams. 
     
     
       6. The method of  claim 1 , further comprising administering a cytokine, or a growth factor, or mixtures thereof. 
     
     
       7. The method of  claim 6 , wherein the growth factor is selected from the group consisting of platelet-derived growth factor, vascular endothelial growth factor, fibroblast growth factor, epidermal growth factor, transforming growth factor-beta, and mixtures thereof. 
     
     
       8. A method for treating a chronic wound of a mammal, which comprises topically administering to the wound a therapeutically effective amount of a mammalian calreticulin comprising natural human calreticulin sequence or natural rabbit calreticulin sequence wherein said calreticulin sequence is directly fused at its N terminus to the C-teminus of a sequence selected from the group consisting of Thr-Met-Glu-Leu-Glu (SEQ ID NO: 8), Met-His-His-His-His-His-His-His-His-Thr-Met-Glu-Leu-Glu (SEQ ID NO: 4), Met-Lys-Lys-Leu-Leu-Phe-Ala-Ile-Pro-Leu-Val-Val-Pro-Phe-Tyr-Ser-His-Ser-Thr-Met-Glu-Leu-Glu (SEQ ID NO: 9), and Met-His-His-His-His-His-His-His-His-Met-Lys-Lys-Leu-Leu-Phe-Ala-Ile-Pro-Leu-Val-Val-Pro-Phe-Tyr-Ser-His-Ser-Thr-Met-Glu-Leu-Glu (SEQ ID NO: 5). 
     
     
       9. The method of  claim 8 , wherein the chronic wound is a chronic diabetic wound. 
     
     
       10. The method of  claim 9 , wherein the chronic diabetic wound is a diabetic foot ulcer. 
     
     
       11. The method of  claim 8 , wherein the calreticulin is administered in an amount between about 0.001 milligram and about 1 gram. 
     
     
       12. The method of  claim 11 , wherein the calreticulin is administered in an amount between about 0.01 milligram and about 50 milligrams. 
     
     
       13. The method of  claim 8 , further comprising administering a cytokine, or a growth factor, or mixtures thereof. 
     
     
       14. The method of  claim 13 , wherein the growth factor is selected from the group consisting of platelet-derived growth factor, vascular endothelial growth factor, fibroblast growth factor, epidermal growth factor, transforming growth factor-beta, and mixtures thereof.